Damaging Drug Study? Bury It

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Damaging Drug Study? Bury It

The risks for children taking some antidepressants could outweigh the benefits, according to an analysis of data that pharmaceutical companies did not make widely available to the public or to researchers.

Researchers in the United Kingdom analyzed 22 randomized controlled trials that compared the effects of antidepressants and placebos in children from 5 to 18 years old. Data on four out of the five antidepressants examined showed the drugs had the potential to do more harm than good in depressed kids, according to research published in the April issue of the British medical journal The Lancet.

About half of the results had not previously been published in medical journals, so researchers and doctors didn't have access to them. The published data showed the drugs benefited young patients with depression. But when the unpublished results were factored in, the risks outweighed the benefits, the researchers said. It's unclear why the studies were not published, but critics accuse pharmaceutical companies of withholding studies that didn't turn out the way they hoped.

"We can't tell what motivates the pharmaceutical companies involved, but we do know that some probably don't publish for that reason, given recent reports," said Dr. Craig Whittington, the lead researcher on the * Lancet* paper and a researcher at the University College of London, referring to a recent study published in the Canadian Medical Association Journal that said executives of GlaxoSmithKline (the maker of Paxil) had advised members of their staff to withhold data about antidepressants' effects on children.

The research in question addressed only children with depression. The drugs might be safe and effective for treating children with obsessive-compulsive disorder, anxiety or other problems, the U.K. researchers said.

Fluoxetine, or Prozac, was the exception. The Lancet analysis found the drug could help depressed children. But evidence on sertraline (Zoloft), citalopram hydrobromide (Celexa) and venlafaxine (Effexor) showed the drugs didn't do the children any good, and might actually be harmful.

The researchers examined the incidence of risk factors as reported in the studies, such as "suicide, suicide attempt, suicidal tendency, non-accidental overdose and thoughts of self harm," Whittington said.

The Lancet study comes in the midst of a debate over whether antidepressant drugs – also called selective serotonin reuptake inhibitors, or SSRIs – might cause some children and adolescents to commit suicide. In 2003, the United Kingdom's Committee on Safety of Medicines prohibited the treatment of childhood depression with any SSRI except Prozac. The U.S. Food and Drug Administration has ordered pharmaceutical companies to include warnings on drug labels, but stopped short of prohibition.

"In view of the high risk of suicide in this group of children and young people, the possibility that a drug might increase that risk without clear evidence of benefit, should, in our view, discourage its use," the authors wrote in The Lancet paper.

Vera Hassner Sharav, founder of the advocacy group Alliance for Human Research Protection, says the FDA has known about the potential suicide risk in children since at least 1996, and that the agency has put children's lives at risk by not disclosing that information.

"How will FDA officials defend their failure to protect children from the hazards of antidepressants before a Congressional committee, inasmuch as they knew the content of the unpublished data for years?" Sharav wrote in an e-mail.

Sharav points out the suicide rate among adolescents has actually increased since SSRI antidepressants have been prescribed for youth. From 1980 to 1997, it increased 11 percent for 10- to 15-year-olds, and 109 percent in kids from 10 to 17 years old, according to the Centers for Disease Control and Prevention.

The House Committee on Energy and Commerce recently warned it might launch an investigation into the FDA for holding back crucial information about the dangers of antidepressants for some children.

"In a global medical culture where evidence-based practice is seen as the gold standard for care, these failings are a disaster," wrote Lancet editors in an editorial accompanying the data analysis.

The FDA, GlaxoSmithKline and Pfizer (maker of Zoloft) did not respond to requests for comment for this article.

"This debate about the SSRIs is overdue," said Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. "We're in a classic situation where because of liberal off-label prescribing practices in the U.S. and heavy direct-to-consumer advertising, we've got basically a load of kids getting drugs for which they've never been tested."

Off-label prescribing is the legal practice of prescribing an FDA-approved drug for disorders other than those for which it has been specifically approved.

But experts also cautioned that it could be even more dangerous to yank fragile children, especially teenagers, off antidepressants when the medication very well might be helping them. The most important part of drug treatment for depression is monitoring its effects and calibrating it accordingly, because everyone's response is different, said Alice Sterling Honig, a psychologist and professor emerita of child development at Syracuse University.

"With a little antidepressant, a little Zoloft or a little Prozac, maybe he'll cheer up enough so psychology can help him," Honig said. "At least it could let him talk to me, because with depression sometimes people don't want to talk at all."